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Steenbergen, R. A. M.

Publications and source records attributed to Steenbergen, R. A. M..

2 recordsLinked to original sources

Ageing of the Upper Airway Epithelial Niche Limits Tissue-Resident T Cell Immunity

Respiratory tract infections are a major cause of morbidity and mortality among older adults worldwide. Yet, how ageing shapes protective immunity within the upper respiratory tract (URT) remains poorly understood. Here, we profiled the nasal immune landscape of young adults and older adults with and without frailty, using high-dimensional cytometry, proteomics, single-cell transcriptomics and T cell receptor (TCR) sequencing. Ageing was associated with a selective reduction of tissue-resident memory T (Trm) cells, independent of effector T cell numbers, inflammageing levels or frailty and was accompanied by a decline in T cell receptor repertoire stability. Trm cells from older adults also showed decreased steady-state IFN{gamma} expression, accompanied by reduced antiviral transcriptional programs in the mucosa. Mechanistically, in vitro PBMC-epithelium co-culture models revealed that older adults have a reduced capacity for Trm differentiation, which was associated with a diminished epithelial TGF-{beta} secretion, driven by reduced expression in ciliated epithelial cells. Together, these findings reveal that URT immunity deteriorates with age due to disrupted epithelial-immune crosstalk. This identifies the epithelial niche as a key regulator of mucosal immune ageing and suggests that enhancing TGF{beta} signaling may improve the effectiveness of mucosal airway vaccination strategies in older populations.

immunology↗

A cell surface proteomic atlas reveals socioeconomic status associated immune diversity

Socioeconomic status (SES) is a potent determinant of immune variation, yet unbiased approaches to holistically map the effect of SES on the immune system are lacking. We developed a high-dimensional flow cytometry-based profiling approach to analyse 331 cell surface proteins across 33 immune cell subsets within an SES-stratified Senegalese cohort, alongside a European cohort (Netherlands). We identified 108 SES-related markers across the immune system, revealing that lower SES individuals exhibited downregulation of surface proteins, affecting in particular adhesins, chemokine and complement receptors. Conversely, lower SES was associated with hallmarks of chronic activation and exhaustion including upregulation of immune checkpoints. Metabolic profiling demonstrated that while lower SES individuals displayed elevated baseline RNA transcription, higher SES individuals exhibited superior protein translation rates. We validated these SES-related immune trends in an independent cohort and provide an interactive online resource for exploring this surface protein atlas on immune cell subsets. Taken together, these findings provide a global overview of how the cell surface proteome varies by SES, and identify molecular changes that can affect vaccine efficacy and disease outcomes.

immunology↗